The goal of the proposed research program is the determination of the molecular basis of interactions between murine ectropic leukemia viruses (MuLV-E) and host cells that mediate virus entry. In preliminary studies, Dr. Albritton has isolated the gene encoding REC1 and identified a 27 amino acid domain that specifies the MuLV host range. REC1 is a multi- membrane spanning protein that was recently shown to be a cationic amino-acid transporter. We further showed that two specific residues within the domain are essential to both virus entry and binding.Three specific aims are listed. Aim 1 proposes: a) to define the virus binding site within the 27 amino acid domain by identifying all the residues that are crucial to viral entry; b) to determine the contribution of the binding site residues to receptor function by examining the virus envelope binding and virus entry capabilities of receptor proteins substituted with biochemically similar and dissimilar amino acids in these proteins. Aim 2 proposes to test the hypothesis that the putative virus binding domain is the single region of the receptor that is essential for virus entry. This will be carried out by placing this domain in other virus receptor and non-receptor membrane proteins. The ability of these chimeric proteins to bind purified virus envelope protein will be measured. Aim 3 proposes to identify specific sites on viral proteins that interact with the receptor. This will be carried out by selecting for mutant viruses that complement the leaky mutation of a receptor with (10-5 fold lower efficiency in indicating virus entry).